Lyme disease is the most common vector-borne disease in the United States, with more than 10,000 reported cases per year. People bitten by ticks infected with Borrelia burgdorferi may develop destructive arthritis, irreversible neurological problems and cardiac conduction defects. The disease is treatable with antibiotics if properly diagnosed at an early stage, but currently available diagnostic reagents are not sufficient for accurate diagnosis. The long term goal of this project is to use a phage display based approach called "epitope discovery" to identify novel peptides for use as diagnostic reagents against Lyme disease. No prior knowledge of antigens association with the disease is required; instead, sera from patients with Lyme disease will be used to affinity-select peptides that react with Lyme disease specific antibodies. Epitope discovery has been successfully tested in a model system; the present project would represent the first attempt to use it to develop diagnostics for a disease for which clinical reagents are truly needed. The specific aims of the proposal are: 1) to discover peptides that bind specifically to antibodies found in patients with Lyme disease, and 2) to develop such peptides for use as diagnostics.